Broad objectives: My major research interest is to achieve a better understanding of congenital anomalies and specifically those of the lungs and cardiovascular system. As a pediatrician I believe that basic knowledge of the normal development of the lung and its nervous and vascular attachments in the vertebrate will help in the diagnosis, treatment, and perhaps prevention of congenital conditions. the proposed research will identify in greater detail the pulmonogenic areas of the chick embryo, even as early as in stages before the formation of the primitive streak. It will trace the migration of the pulmonogenic cells into the lungs; anatomical, histological and biochemical factors involved in formation and subdivision of the lung buds; and the behavior of the pulmonogenic areas when separated from their normal environment. Methodology: I will continue to use radioactive graft implantation to detail the early movements of organogenesis. Later movements and growth of the lung buds will be analyzed by fiber marking (mapping) of the lung rudiments. Innervation of the lung will be studied by histochemical observations in sectioned embryos. The development of normal bronchial and vascular patterns will be investigated by gross and microscopic study of early and latex injected older specimens, and coordinated with a collection of mature lungs. The sinoatrial region of chick and human embryos will be dissected to learn the relation of fiber patterns to rotation of splanchnic mesoderm (lung and heart) during early morphogenesis. Details of the interaction of prelung endoderm and mesoderm will be studied in vitro after each group of cells has been grown in culture; this information will be coordinated with the appearance of lung-specific molecules, products of morphogenetic change (ATP, cyclic AMP, total protein and phosphodiesterase activity) and morphogens in pooled fragments that represent different portions of the lung anlage and adjacent endoderm and mesoderm tissue. The effects of ablating the vascular and neuronal supply to the developing lung and cardiovascular system will be observed and analyzed.